Lanolin-Based Synthetic Membranes for Transdermal Permeation and Penetration Drug Delivery Assays

Due to the high similarity in composition and structure between lanolin and human SC lipids, we will work with two models from wool wax. Two types of lanolin were evaluated: one extracted with water and surfactants (WEL) and the other extracted with organic solvents (SEL). Skin permeation and skin penetration studies were performed with two active compounds to study the feasibility of the use of lanolin-based synthetic membranes as models of mammalian skin. Diclofenac sodium and lidocaine were selected as the active compounds considering that they have different chemical natures and different lipophilicities. In the permeation assay with SEL, a better correlation was obtained with the less permeable compound diclofenac sodium. This assay suggests the feasibility of using artificial membranes with SEL as a model for percutaneous absorption studies, even though the lipophilic barrier should be improved. Penetration profiles of the APIs through the SEL and WEL membranes indicated that the two membranes diminish penetration and can be considered good membrane surrogates for skin permeability studies. However, the WEL membranes, with a pH value similar to that of the skin surface, promoted a higher degree of diminution of the permeability of the two drugs, similar to those found for the skin.

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The factors determining the skin penetration and cellular uptake of nanocarriers: New hope for clinical development

Current Pharmaceutical Design ◽

10.2174/1381612827666210810091745 ◽

2021 ◽

Vol 27 ◽

Author(s):

Afsaneh Farjami ◽

Sara Salatin ◽

Samira Jafari ◽

Mohammad Mahmoudian ◽

Mitra Jelvehgari

Keyword(s):

Drug Delivery ◽

Skin Permeation ◽

Direct Interaction ◽

Skin Barrier ◽

Skin Penetration ◽

Physicochemical Characteristics ◽

Skin Permeability ◽

Topical Drug Delivery ◽

Major Barrier ◽

Composition And Structure

: The skin provides a protective barrier against toxic environments and also offers a valuable route for topical drug delivery. The stratum corneum (SC) is the outermost layer of the skin and serves as the major barrier to chemical transfer through the skin. The human skin barrier is particularly diffcult to overcome because of the complex composition and structure of the SC. Nanoparticulate carriers have gained widespread attention in topical drug delivery due to their tunable and versatile properties. The present review summarizes the main factors involved in the skin penetration of nanocarriers containing drug. Employment of nanotechnology in topical delivery has grown progressively during recent years; however, it is important to monitor the skin penetration of nanocarriers prior to their use due to avoid possible toxic effects. Nanocarriers can act as a means to increase the skin permeation of drugs by supporting a direct interaction with the SC and increasing the period of permanence on the skin. The skin penetration is influenced by the physicochemical characteristics of nanocarriers such as composition, size, shape, surface chemistry as well as skin features. Considering that the target of topical systems based on nanocarriers is the penetration of therapeutic agents in the skin layers, so a detailed understanding of the factors influencing skin permeability of nanocarriers is essential for safe and efficient therapeutic applications.

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The Influence of Formulation and Excipients on Propranolol Skin Permeation and Retention

BioMed Research International ◽

10.1155/2018/1281673 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Cristina Padula ◽

Sara Nicoli ◽

Silvia Pescina ◽

Patrizia Santi

Keyword(s):

Skin Permeation ◽

Skin Penetration ◽

Infantile Hemangioma ◽

Skin Surface ◽

Time Frame ◽

Systemic Absorption ◽

Therapeutic Drug ◽

Topical Formulations ◽

Skin Retention

The objective of this work was to study in vitro propranolol permeation and skin retention after topical application of different semisolid vehicles, with the final aim of developing new topical formulations intended for the treatment of infantile hemangioma, able to produce therapeutic drug levels in the skin, avoiding systemic absorption. Propranolol ointments, creams, and gels were prepared and tested on pig skin, an accepted model of human skin. From the results obtained in the present work it is clear that the permeation of propranolol across the skin is a poor predictor of its skin retention, at least in the time-frame considered. With an application time of 4 h, reasonably close to the permanence time of a semisolid formulation on the skin surface, the best performance (high retention and low skin penetration) was obtained with lipophilic formulations, in particular with a lipophilic cream containing olive oil. Hydrophilic formulations, such as gels, are characterized by a significant permeation across the skin, probably leading to systemic side effects, accompanied by a limited skin retention. Overall, the results obtained in the present work pose the basis for the development of new topical formulations, containing propranolol, with better performance and reduced systemic absorption.

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The Effect of Alkyl Chain Number in Sucrose Surfactant on the Physical Properties of Quercetin-Loaded Deformable Nanoliposome and Its Effect on In Vitro Human Skin Penetration

Nanomaterials ◽

10.3390/nano8080622 ◽

2018 ◽

Vol 8 (8) ◽

pp. 622 ◽

Cited By ~ 5

Author(s):

In Ki Hong ◽

Ji Hoon Ha ◽

Sangkeun Han ◽

Hakhee Kang ◽

Soo Nam Park

Keyword(s):

Human Skin ◽

Alkyl Chain ◽

Skin Permeation ◽

Entrapment Efficiency ◽

Skin Penetration ◽

Skin Permeability ◽

Non Invasive ◽

Edge Activator

Non-invasive skin penetration of a drug is increased by an edge activator, which enhances the nanoliposome deformability. The objective of this study was to investigate the role of the alkyl chain number of sucrose surfactants as an edge activator in elastic nanoliposomes. In addition, the physicochemical properties of the elastic nanoliposomes were characterized and an in vitro human skin permeation study was performed. Elastic nanoliposomes that were composed of sucrose monostearate (MELQ), sucrose distearate (DELQ), and sucrose tristearte (TELQ) were prepared using a thin-film hydration method. Particle size and entrapment efficiency of elastic nanoliposomes increased proportionally with an increase in the amounts and the numbers of the stearate in sucrose surfactant. Deformability of elastic nanoliposomes was indicated as DELQ > MELQ > TELQ and the same pattern was revealed through the in vitro human skin permeability tests. These results suggest that the number of alkyl chains of sucrose surfactant as edge activator affects the physicochemical property, stability, and skin permeability in elastic nanoliposome. Our findings give a valuable platform for the development of elastic nanoliposomes as skin drug delivery systems.

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Graphene Oxide Topical Administration: Skin Permeability Studies

Materials ◽

10.3390/ma14112810 ◽

2021 ◽

Vol 14 (11) ◽

pp. 2810

Author(s):

Filipa A. L. S. Silva ◽

Raquel Costa-Almeida ◽

Licínia Timochenco ◽

Sara I. Amaral ◽

Soraia Pinto ◽

...

Keyword(s):

Graphene Oxide ◽

Photothermal Therapy ◽

Near Infrared ◽

Skin Permeation ◽

Pharmaceutical Formulations ◽

Topical Administration ◽

Skin Permeability ◽

Large Size ◽

Low Toxicity ◽

Permeability Studies

Nanostructured carriers have been widely used in pharmaceutical formulations for dermatological treatment. They offer targeted drug delivery, sustained release, improved biostability, and low toxicity, usually presenting advantages over conventional formulations. Due to its large surface area, small size and photothermal properties, graphene oxide (GO) has the potential to be used for such applications. Nanographene oxide (GOn) presented average sizes of 197.6 ± 11.8 nm, and a surface charge of −39.4 ± 1.8 mV, being stable in water for over 6 months. 55.5% of the mass of GOn dispersion (at a concentration of 1000 µg mL−1) permeated the skin after 6 h of exposure. GOn dispersions have been shown to absorb near-infrared radiation, reaching temperatures up to 45.7 °C, within mild the photothermal therapy temperature range. Furthermore, GOn in amounts superior to those which could permeate the skin were shown not to affect human skin fibroblasts (HFF-1) morphology or viability, after 24 h of incubation. Due to its large size, no skin permeation was observed for graphite particles in aqueous dispersions stabilized with Pluronic P-123 (Gt–P-123). Altogether, for the first time, Gon’s potential as a topic administration agent and for delivery of photothermal therapy has been demonstrated.

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Comparison of Synthetic Membranes to Heat-Separated Human Epidermis in Skin Permeation Studies In Vitro

Pharmaceutics ◽

10.3390/pharmaceutics13122106 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2106

Author(s):

Anita Kovács ◽

Stella Zsikó ◽

Fanni Falusi ◽

Erzsébet Csányi ◽

Mária Budai-Szűcs ◽

...

Keyword(s):

Gold Standard ◽

Skin Permeation ◽

Diclofenac Sodium ◽

Human Epidermis ◽

Formulation Development ◽

Early Screening ◽

Synthetic Membranes ◽

Screening Model ◽

Permeation Studies

In recent years, the study of dermal preparations has received increased attention. There are more and more modern approaches to evaluate transdermal formulations, which are crucial in proving the efficacy of a formulation. The aim of this study was to compare permeation across innovative synthetic membranes (Strat-M and Skin PAMPA membranes) and heat-separated human epidermis (HSE, gold standard membrane) using four different dermal formulations. The Strat-M and Skin PAMPA membranes were designed to mimic the stratum corneum layer of the human epidermis. There have also been some publications on their use in dermal formulation development, but further information is needed. Drug permeation was measured using formulations containing diclofenac sodium (two hydrogels and two creams). The HSE, Strat-M, and Skin PAMPA membranes proved to be significantly different, but based on the results, the Strat-M membrane showed the greatest similarity to HSE. The permeation data of the different formulations across different membranes showed good correlations with formulations similar to these four, which allows the prediction of permeation across HSE using these synthetic membranes. In addition, Strat-M and Skin PAMPA membranes have the potential to select and differentiate a dermal formulation containing diclofenac sodium as an early screening model.

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Graphene Oxide Topical Administration: Skin Permeability Studies

10.20944/preprints202103.0550.v1 ◽

2021 ◽

Author(s):

Filipa A. L. S. Silva ◽

Raquel Costa-Almeida ◽

Licínia Timochenco ◽

Sara I. Amaral ◽

Soraia Pinto ◽

...

Keyword(s):

Graphene Oxide ◽

Photothermal Therapy ◽

Near Infrared ◽

Skin Permeation ◽

Pharmaceutical Formulations ◽

Topical Administration ◽

Skin Permeability ◽

Large Size ◽

Low Toxicity ◽

Permeability Studies

Nanostructured carriers have been widely used in pharmaceutical formulations for dermatological treatment. They offer targeted drug delivery, sustained release, improved biostability, and low toxicity, usually presenting advantages over conventional formulations. Due to its large surface area, small size and photothermal properties, graphene oxide (GO) has the potential to be used for such applications. Nanographene oxide (GOn) presented average sizes of 197.6 ± 11.8 nm, and a surface charge of -39.4 ± 1.8 mV, being stable in water for over 6 months. 55.5 % of the mass of GOn dispersion (at a concentration of 1 mg mL-1) permeated the skin after 6 h of exposure. GOn dispersions have been shown to absorb near-infrared radiation, reaching temperatures up to 45.7 °C, within mild photothermal therapy temperature range. Furthermore, GOn in amounts superior to those which could permeate the skin were shown not to affect human skin fibroblasts (HFF-1) morphology or viability, after 24 h of incubation. Due to its large size, no skin permeation was observed for graphite particles in aqueous dispersions stabilized with Pluronic P-123 (Gt-P-123). Altogether, for the first time, GOn potential as a topic administration agent and for delivery of photothermal therapy has been demonstrated.

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Nanotechnological Innovations Enhancing the Topical Therapeutic Efficacy of Quercetin: A Succinct Review

Current Drug Delivery ◽

10.2174/1567201817666200317123224 ◽

2020 ◽

Vol 17 (4) ◽

pp. 270-278

Author(s):

Maha Nasr ◽

Rawan Al-Karaki

Keyword(s):

Side Effects ◽

Therapeutic Efficacy ◽

Skin Permeation ◽

Skin Penetration ◽

Topical Delivery ◽

Natural Compounds ◽

Therapeutic Activity ◽

Dermatological Diseases ◽

Anti Inflammatory ◽

Topical Applications

Nanotechnology is currently a hot topic in dermatology and nutraceutical/cosmeceutical delivery, owing to the advantages it provides in terms of enhancing the skin permeation of drugs, as well as increasing their therapeutic efficacy in the treatment of different dermatological diseases. There is also a great interest in the topical delivery of nutraceuticals; which are natural compounds with both therapeutic and cosmetic benefits, in order to overcome the side effects of topically applied chemical drugs. Quercetin is a key nutraceutical with topical antioxidant and anti-inflammatory properties which was reported to be effective in the treatment of different dermatological diseases, however, its topical therapeutic activity is hindered by its poor skin penetration. This review highlights the topical applications of quercetin, and summarizes the nanocarrier-based solutions to its percutaneous delivery challenges.

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Omega-3- and Resveratrol-Loaded Lipid Nanosystems for Potential Use as Topical Formulations in Autoimmune, Inflammatory, and Cancerous Skin Diseases

Pharmaceutics ◽

10.3390/pharmaceutics13081202 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1202

Author(s):

Ana R. Caldas ◽

José Catita ◽

Raul Machado ◽

Artur Ribeiro ◽

Fátima Cerqueira ◽

...

Keyword(s):

Skin Diseases ◽

Skin Permeation ◽

Chemical Properties ◽

Topical Administration ◽

Skin Surface ◽

Lipid Nanoparticles ◽

Skin Layer ◽

No Production ◽

Omega 3 ◽

Pharmaceutical Industries

Resveratrol (RSV) and omega 3 (ω3), because of their biological favorable properties, have become subjects of interest for researchers in dermocosmetic and pharmaceutical industries; however, these bioactives present technological limitations that hinder their effective delivery to the target skin layer. To overcome the stability and skin permeation limitations of free bioactives, this work proposes a combined strategy involving two different lipid nanosystems (liposomes and lipid nanoparticles) that include ω3 in their lipid matrix. Additionaly, RSV is only encapsulated in liposomes that provid an adequate amphiphilic environment. Each formulation is thoroughly characterized regarding their physical–chemical properties. Subsequently, the therapeutic performance of the lipid nanosystems is evaluated based on their protective roles against lipid peroxidation, as well as inhibition of cicloxygenase (COX) and nitric oxid (NO) production in the RWA264.7 cell line. Finally, the lipid nanosystems are incorporated in hydrogel to allow their topical administration, then rheology, occlusion, and RSV release–diffusion assays are performed. Lipid nanoparticles provide occlusive effects at the skin surface. Liposomes provide sustained RSV release and their flexibility conferred by edge activator components enhances RSV diffusion, which is required to reach NO production cells and COX cell membrane enzymes. Overall, the inclusion of both lipid nanosystems in the same semisolid base constitutes a promising strategy for autoimmune, inflammatory, and cancerous skin diseases.

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Topical Artocarpus communis Nanoparticles Improved the Water Solubility and Skin Permeation of Raw A. communis Extract, Improving Its Photoprotective Effect

Pharmaceutics ◽

10.3390/pharmaceutics13091372 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1372

Author(s):

Chun-Yin Yang ◽

Pao-Hsien Huang ◽

Chih-Hua Tseng ◽

Feng-Lin Yen

Keyword(s):

Water Solubility ◽

Methanol Extract ◽

Biological Effects ◽

Skin Permeation ◽

Environmental Pollutants ◽

Skin Penetration ◽

Physicochemical Characteristics ◽

The Poor ◽

Deep Layers ◽

Poor Water Solubility

Antioxidants from plant extracts are often used as additives in skincare products to prevent skin problems induced by environmental pollutants. Artocarpus communis methanol extract (ACM) has many biological effects, such as antioxidant, anti-inflammatory, wound healing, and photoprotective effects; however, the poor water solubility of raw ACM has limited its applications in medicine and cosmetics. Topical antioxidant nanoparticles are one of the drug-delivery systems for overcoming the poor water solubility of antioxidants for increasing their skin penetration. The present study demonstrated that ACM-loaded hydroxypropyl-β-cyclodextrin and polyvinylpyrrolidone K30 nanoparticles (AHP) were successfully prepared and could effectively increase the skin penetration of ACM through changing the physicochemical characteristics of raw ACM, including reducing the particle size, increasing the surface area, and inducing amorphous transformation. Our results also revealed that AHP had significantly better antioxidant activity than raw ACM for preventing photocytotoxicity because the AHP formulation increased the cellular uptake of the ACM in UVB-irradiated HaCaT keratinocytes. In conclusion, our results suggest that AHP may be used as a good topical antioxidant nanoparticle for delivering ACM into deep layers of the skin for preventing UVB-induced skin problems.

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Transcutol® P Containing SLNs for Improving 8-Methoxypsoralen Skin Delivery

Pharmaceutics ◽

10.3390/pharmaceutics12100973 ◽

2020 ◽

Vol 12 (10) ◽

pp. 973

Author(s):

Giulia Pitzanti ◽

Antonella Rosa ◽

Mariella Nieddu ◽

Donatella Valenti ◽

Rosa Pireddu ◽

...

Keyword(s):

Skin Permeation ◽

Spherical Shape ◽

Entrapment Efficiency ◽

Skin Layer ◽

Skin Permeability ◽

Puva Therapy ◽

Ultraviolet A ◽

3T3 Fibroblasts ◽

Skin Delivery

Topical psoralens plus ultraviolet A radiation (PUVA) therapy consists in the topical application of 8-methoxypsoralen (8-MOP) followed by the skin irradiation with ultraviolet A radiation. The employment of classical 8-MOP vehicles in topical PUVA therapy is associated with poor skin deposition and weak skin permeability of psoralens, thus requiring frequent drug administration. The aim of the present work was to formulate solid lipid nanoparticles (SLNs) able to increase the skin permeation of 8-MOP. For this purpose, the penetration enhancer Transcutol® P (TRC) was added to the SLN formulation. SLNs were characterized with respect to size, polydispersity index, zeta potential, entrapment efficiency, morphology, stability, and biocompatibility. Finally, 8-MOP skin diffusion and distribution within the skin layers was investigated using Franz cells and newborn pig skin. Freshly prepared nanoparticles showed spherical shape, mean diameters ranging between 120 and 133 nm, a fairly narrow size distribution, highly negative ζ potential values, and high entrapment efficiency. Empty and loaded formulations were almost stable over 30 days. In vitro penetration and permeation studies demonstrated a greater 8-MOP accumulation in each skin layer after SLN TRC 2% and TRC 4% application than that after SLN TRC 0% application. Finally, the results of experiments on 3T3 fibroblasts showed that the incorporation of TRC into SLNs could enhance the cellular uptake of nanoparticles, but it did not increase their cytotoxicity.

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